Dose-Dependent Solubility-Permeability Interplay for Poorly Soluble Drugs under Non-Sink Conditions

We investigated the solubility-permeability interplay using a solubilizer additive under non-sink conditions. Sodium lauryl sulfate (SLS) was used as a solubilizer additive. The solubility and permeability of two poorly soluble drugs at various doses, with or without SLS, were evaluated by flux measurements. The total permeated amount of griseofulvin, which has high permeability, increased by the addition of SLS. On the other hand, triamcinolone, which has low permeability, showed an almost constant rate of permeation regardless of the SLS addition. The total permeated amount of griseofulvin increased by about 20-30% when the dose amount exceeded its solubility, whereas its concentration in the donor chamber remained almost constant. However, the total permeated amount of triamcinolone was almost constant regardless of dose amount. These results suggest that the permeability of the unstirred water layer (UWL) may be affected by SLS and solid drugs for high-permeable drugs. The effect of solid drugs could be explained by a reduction in the apparent UWL thickness. For the appropriate evaluation of absorption, it would be essential to consider these effects.

Automated summary

The study found that using solubilizer additive SLS under non-sink conditions can increase the total permeated amount of high-permeable drugs, while not significantly affecting the permeation rate of low-permeable drugs. Even exceeding solubility, the total permeated amount of high-permeable drugs would increase, while that of low-permeable drugs remains almost constant.